1561810-52-3Relevant academic research and scientific papers
Double-ring heterocyclic amines Hedgehog signal pathway inhibitor
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, (2018/06/14)
The invention relates to the field of biological medicine, and concretely relates to bicyclic heterocyclic amine compounds, and the compounds are a new Hedgehog inhibitor and pharmaceutically acceptable salts shown as a general formula (I). The compounds can be used as a Hedgehog signal conduction inhibitor applied to multiple medical applications.
Novel 4-(2-pyrimidinylamino)benzamide derivatives as potent hedgehog signaling pathway inhibitors
Xin, Minhang,Zhang, Liandi,Tu, Chongxing,Tang, Feng,Wen, Jun
, p. 5029 - 5036 (2018/09/27)
A series of novel hedgehog signaling pathway inhibitors have been designed and synthesized based on our previously reported scaffold of 4-(2-pyrimidinylamino)benzamide. The Hh signaling pathway inhibitory activities were evaluated by Gli-luciferase reporter method and most compounds showed more potent inhibitory activities than vismodegib. Three compounds were picked out to evaluated in vivo for their PK properties, and compound 23b bearing a 2-pyridyl A-ring and (morpholin-4-yl)methylene at 3-position of D-ring demonstrated satisfactory PK properties. This study suggested the 4-(2-pyrimidinylamino)benzamides were a series of potent Hh signaling pathway inhibitors, deserving to further structural optimization.
Design, synthesis, and evaluation of pyrrolo[2,1-f][1,2,4]triazine derivatives as novel hedgehog signaling pathway inhibitors
Xin, Minhang,Zhang, Liandi,Tang, Feng,Tu, Chongxing,Wen, Jun,Zhao, Xinge,Liu, Zhaoyu,Cheng, Lingfei,Shen, Han
, p. 1429 - 1440 (2014/03/21)
A novel series of Hh signaling pathway inhibitors were designed by replacing the pyrimidine skeleton of our earlier reported lead compound 1 with pyrrolo[2,1-f][1,2,4]triazine scaffold. Starting from this new scaffold, SAR exploration was investigated based on structural modification on A-ring, C-ring and D-ring. And several much potent compounds were studies in vivo to profile their pharmacokinetic properties. Finally, optimization leads to the identification of compound 19a, a potent Hh signaling pathway inhibitor with superior potency in vitro and satisfactory pharmacokinetic properties in vivo.
Five-membered heteroaromatic ring fused-pyrimidine derivatives: Design, synthesis, and hedgehog signaling pathway inhibition study
Zhang, Liandi,Xin, Minhang,Shen, Han,Wen, Jun,Tang, Feng,Tu, Chongxing,Zhao, Xinge,Wei, Ping
, p. 3486 - 3492 (2014/07/22)
A series of novel five-membered heteroaromatic ring fused-pyrimidine derivatives including purines, pyrrolo[2,3-d]pyrimidines, pyrrolo[3,2-d] pyrimidines, thieno[2,3-d]pyrimidines, thieno[3,2-d]pyrimidines and furo[3,2-d]pyrimidines have been identified to be potent inhibitors of hedgehog signaling pathway. The synthesis and SAR of these compounds are described. Among this new series of hedgehog signaling pathway inhibitors, most compounds exhibited significant inhibitory activity compared to vismodegib, indicating that the five-membered heteroaromatic ring fused-pyrimidines stand out as encouraging scaffolds among the currently reported structural skeletons for hedgehog signaling pathway inhibitors, deserving more exploration and further investigation.
